Hey, everyone, welcome to the Peter Attea drive. I'm your host, Peter, into you. Theo Drive is a result of my hunger for optimizing performance, health longevity, critical thinking, along with a few other obsessions along the way. I've spent the last several years working with some of the most successful top performing individuals in the world, and this podcast is my attempt to synthesize what I've learned along the way to help you live a higher quality, more fulfilling life. If you enjoy this podcast, you can find more information on today's episode and other topics at Peter tia MD dot com. Everybody welcome to this week's episode of the drive. I'd like to take a couple of minutes to talk about why we don't run ads on this podcast and why.

Instead, we've chosen to rely entirely on listener support. If you're listening this, you probably already know. But the two things I care most about professionally are how to live longer and how to live better have a complete fascination and obsession with this topic. I practice it professionally, and I've seen firsthand how access to information is basically all people need to make better decisions and improve the quality of their lives curating and sharing this knowledge is not easy. And even before starting the podcast, that became clear to me. The sheer volume of material published in this space is overwhelming. I'm fortunate to have a great team that helps me continue learning and sharing this information with you. To take one example, our show notes are in a league of their own. In fact, we now have a full time person that is dedicated to producing those. And the feedback has mirrored this.

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And as I said, we're not taking ad dollars from anyone. But instead, what I'd like to do is work with companies who make the products that I already love and would already talk about for free and have them past savings on to you again. The podcast will remain free to all. But my hope is that many of you will find enough value in one the podcast itself and to the additional content exclusive for members to support us at a level that makes sense for you. I want to thank you for taking a moment to listen to this. If you learn from and find value in the content I produce, please consider supporting us directly by signing up for a monthly subscription. Welcome to the kickoff of this Matthew Walker three part series on sleep. This is one of the topics were asked about the most, and I think this will be a fan favorite. This series of podcast will be released over three weeks, with this one being the first now, at the end of the series, we're going to take questions for a follow up A m A,

with Matthew asking questions on the A. M A Forum and listening to the A M. A podcast with Matthew, along with all AM AIDS, will only be available to subscribers. So if you haven't signed up yet, you can do so now at Peter Attea, MD dot com forward slash subscribe. I guess this week is Matthew Walker, professor of neuroscience and psychology at the University, California, Berkeley, and the founder and director of the Center for Human Sleep Science. Matthew earned his undergraduate degree and PhD in neurophysiology in London and subsequently became a professor of psychiatry at Harvard Medical School before moving to Berkeley. His research examines the impact of sleep on human brain function in healthy and disease populations. Today he has published over 100 scientific studies.

He has received numerous funding awards from the National Science Foundation, National Institutes of Health, and he's a fellow of the National Academy of Sciences. He's the author of the international bestseller Why We Sleep, which also happens to be the favorite book of my not yet two year old son. He holds many patents covering various consumer base sleep recordings, sleep tracking and sleep simulation. He's asleep scientist at Google, where he helps the scientific exploration of sleep in health and disease. He is also an enormous fan of Formula One and my hero, Ireton Santa. And in the third part of this installment, we actually spend quite a bit of time discussing this here. In the first part of this series, we discuss the relationship between sleep, dementia and Alzheimer's disease,

the four pillars of sleep, sleep stages, measurements and the overall importance of sleep, the lack of sleep and dangers of drowsy driving and how the conversation of sleep has changed over the past several years. So without further delay, here is the first installment of my three part series with professor Matthew Walker. Thank you so much for making time to meet on a Sunday

absolute privilege, and it delight

to be with you. Pete, What's with the weather in Berkeley? Is it always this bad?

Okay, now, when Peter says it always this bad, it's probably in the low sixties, and it's there isn't much blue sky. It's dry and there's a very pleasant breeze and there is some wonderful blossom. So I know it's not San Diego. Everything is utopian, and people listening come by are at the end of the day and holding hands. But it's pretty good day when you consider it's still February,

right? I know it's like I live in these extremes, like, you know, in San Diego, the bars like it has to be perfect. And then in New York, you just sort of expected to be sort of, you know, like I was there two days ago. It's stuck.

I mean, all three of those, the best in the United Kingdom, you know, my home country were essentially have nine months of really bad weather and then three months of winter. And then that's your you know, that's your year. So this today, February like this low sixties. I'm

a happy man. I came from Canada, where it's bad in a different way. But the first time I saw California was my interview for med school, and it was a February day and it was 76 degrees and I was the first time it occurred to me that you didn't have to suffer, you know, like I just I never realized I mean, I guess, intellectually, I understood that it could be warm in the winter, but I never occurred to me that you could choose to do that. So Well, now, speaking of this, so what brought you to the U. S? It

was science. I did all of my education backing and like to kingdom, I actually started off at medical school. So back in the UK, at aged 18 you can actually go to medical school 25 year program. And after about two years, this wonderful professor came up and said, Look, you're a nice guy, but you're always asking questions and you're asking them. I think genuinely you're not asking to be on us. But I think you're actually a scientist, not a doctor, because at the time, you know he was thinking doctors air interested in answers. Scientists are interested in questions. I think you're a scientist,

not a doctor. So we didn't have MD PhD programs back at that time. So then, you know, I thought about it for the summer came back, switched neuro science. So essentially brain science did. That was an undergraduate, then went on to do my PhD at the Medical Research Council in London and then came to Harvard for my first faculty position there on Dhe. I was there for seven years as faculty in psychiatry at Harvard on DDE. The winters just got to me and, you know, the environment times as well. Academic was perhaps more combative and competitive, and I think that's one way to bring productivity in a department, and I'm not shaking a finger at it.

But by nature, I'm just a person who is much more collaborative and collegial rather than combative and competitive. So Berkeley fit. My mentality better came out here. Whether was great California. It's an immense, the easy place to arrive in a very difficult place to leave, and I think I probably

won't I know that feeling. I'm probably leaving California. I'm going through the mourning process of accepting a departure because you're you'll be fast. It's a hard place to leave. When did the switch sort of flip in terms of your passion for sleep?

I think back at medical school, I was always interested in states of consciousness. I guess you would describe it as I was fascinated by anesthesia, was fascinated by even hypnosis. I remember actually went out to meet this hypnotist to try and understand not, you know, the act on the show. I wasn't interested in that. I fundamentally wanted to understand. What did he think happened within the brain to produce this altered state of consciousness. So I got really interested in how the brain can switch between sort of state's mental states and then just fundamental awareness states that then naturally led me to just fascinated by sleep. I mean, there is no better demonstration off a gigantic shift in conscious state that happens Toa almost every single living creature on this planet every 24 hours. And back then, this was 20 years ago. We had this fundamental question. Why do we sleep?

And what was staggering to me is that it took 1/3 of our lives. Every species that we've studied to date does it sleeps. It seems to have evolved with life itself on this planet. Even more, we've understood the functions of the other main biological drives eating, drinking and procreating for tens, if not hundreds of years. But the fourth main biological drive, the drive to sleep, had continued to elude scientific judgment. How is that possible? And back then, 20 years ago, if someone were to ask you, you know, why do we sleep?

The crafts answer was, We sleep to cure sleepiness, and that's the fatuous equivalent of saying, Well, we eat to cure hunger. Well, that tells you nothing about the fundamental nutritional benefits off macro nutrition. But that's where we were at with sleep. So it was for me. This perfect collision off fascination in an innate biological problem and universal behavior conserved across evolution together with the fact that we did it for 1/3 of our lives, plus the fact that science had not being able to crack this this note. It was one of the last great remaining scientific mysteries. I thought, Well, you know, if you want to pick something that's going to sustain you for the rest of your life.

And some of the most acerbic, brilliant minds in science had tried to crack this note and failed, including Francis Crick, wonderful scientists who discovered the helical structure of DNA it's unlikely I'm going to do it in my lifetime. But at least it will sustain me as a problem and I could not let it go. And so that was where the intellectual bite happened. The date of the empirical scientific bite happened when I was doing my PhD. I was studying brain wave patterns in people with dementia, and I was trying to do differential diagnosis very early on in the course of cognitive decline. Seeing which type of dementia did they have? Was it frontal lobe dementia? Was it Lewy body dementia? Was it Alzheimer's dementia? And I was failing miserably. For two years. I was killing nothing.

It used to go home. I was living in this doctor's residents had this sort of in the middle of my room, this little igloo of journals that used to sit in on a Sunday, just this kind of like, sort of sanctified circle of knowledge. And I was reading one Sunday and I realized that the different pathologies in these different dementia is some would hit the sleep centers on others would leave those sleep centers completely untouched,

even within forms of dementia that clinically presented. Very similarly

That's right. Yeah. You could see certain brain stem nuclei, certain centers within the basic base of the brain. Some of those were getting eroded by the dementia and those asleep generating centers. Whilst another of those pathologies, those centers were spurred until very late in the disorder. So they probably weren't affecting my early patients. So I realized I was measuring the brain wave activity at the wrong time. I was measuring my patients whilst they were awake. What I should have bean doing is measuring them whilst they were sleep. Got a small grant, set up a sleep lab, learned how to do it, got some great results. And then the question became, If the sleep ist so disrupted,

is it not just a symptom of dip dementia? I could sleep disruption, actually be a biomarker off dementia. Could it? Actually, four tell when you're going to develop dementia and which type or even more profound, is sleep disruption on underlying cause off Alzheimer's disease. And I think right now, based on the weight of the data that we have from we and others have got large research programs doing this work. The evidence, I think, is causal I think that sleep at this stage, maybe one of the most significant lifestyle factors, at least that determines your risk ratio for Alzheimer's disease. I feel the causal evidence for that now in humans and animals is strong enough to make that statement, and I don't make that statement lightly.

Yeah, that is profound, because when you think about the other really big ones vascular disease and insulin resistance, they both feed into a very similar mechanism, which is no ronel energy deprivation. That's right. So do you think that sleep disruption or poor sleep? And I want to come back to the semantics around that? Because I don't actually think I'm well equipped to talk about this intelligently. But do you think that that also disrupts some aspect of energy metabolism in the brain? Or where in the sort of chain of events do you think that that impacts?

I think one of the places that it impacts is in oxidative stress. They think it's safe to say that wakefulness is low level brain damage, and we need sleep to avert some of that low level brain damage. That week for sleep is the price that we pay for wakefulness. Essentially. And you know something I mentioned in a book that I put out was

just a little book, just just a little. Just a little New York Times best seller. Yeah, which, by the way, before we're done. I brought my copy because my youngest son, who's named after our mutual favorite race car driver, loves moons. It's all he thinks about moving smooth every his pajamas, moons everything. And he loves your book, except for the fact that on the inside there are no pictures of moons. So he'll sit there and he'll look at the cover to go. Move, move, move. And then he flips through it. And I get so frustrated that there's no moon pictures inside.

I will course correct that if there's a second edition and I will just try to place the words underneath that it is full the benefit of your But in the book, you know, I proposed that we didn't evolve sleep that perhaps we've got it the wrong way round. Perhaps the default state of life on the planet was sleep, and it was from sleep that wakefulness emerged. Wow, Why could it not have bean that way now, I don't have any good evidence to support my hypothesis. I think it could be utter nonsense, but I think it's a tenable hypothesis. It's just one that's difficult to test. But to come back to your question about Alzheimer's, which I think is critical, I think the first thing is that we see that with insufficient sleep, you get increases in oxidative stress. Those oxidative stress processes lead to a whole cascade of kind of finger flick domino effect off things that lead to neuronal death. One of the areas in the brain that is most sensitive to that is an area that we call the hippocampus,

which is a critical memory center. It's probably one of the first structures to undergo damage in Alzheimer's disease. It's part of the reason why the sort of the FINA type of Alzheimer's is forgetfulness, problems with memory. I think perhaps the stronger evidence, though, in terms of sleep and Alzheimer's disease risk is a remarkable discovery that was made probably about five or six years ago now by some folks at Rochester University in rats, and what they discovered is that the brain actually has a sewage system inside of it. Now your body has one that you're all familiar with, called the lymphatic system, but it turns out the brain has one. It's called the glimpse static system, named after the cells in the brain that formed this system called the glial cells, also known by sort of from a Greek derivative meaning glue. So they used to be just thought as the sort of the South

sort of irrelevant stuff between the neuron.

Exactly. You know, it was like junk, D N A. And of course, what we always learn is that Mother Nature is far too efficient toe leave inefficiency on the table like glue or junk, and it turns out they form this sanitization system within the brain. And what happens, they discovered, is that when you go into deep sleep at night, this sewage system kicks into high gear. And essentially, those glial cells, which surround the brain cells themselves, the neurons proper. They shrink in size by up to 200% and then all of a sudden it leaves a vast amount of room for cerebrospinal fluid to stop refusing the brain and washing out that to try the metabolic detritus off wakefulness, so it would be like New York City.

At night, all of the building shrunk down to 200%. You know, they became miniaturized. And then there was this big effluent flush that just happened across Manhattan to clear out all the debris. And it's essentially good night sleep clean that you get this power cleanse at night. Why is this related to Alzheimer's? Well, one of the critical ingredients that they found that the lymphatic system washed away waas, a sticky toxic protein called Peter Emma Lloyd beater Amyloid is probably one of the two core proteins that we know underlie your risk for the development of Alzheimer's ago. If you're not getting your sleep at night, you're not getting that washing away of the toxic Alzheimer's protein every night. Then you're building up more amyloid within the brain. If you keep doing that night after night, it's like compounding interest on a loan. It's just escalating your Alzheimer's risk. That's why we can then explain the associational evidence, which I don't like associational evidence in epidemiological studies. And I don't think you're a huge fan of it. Perhaps either.

Just don't tell anybody at the Harvard School of Public Health.

Yeah, or maybe the N I H. And I'm applying for grants for everything. But what we certainly see is that if you book it people into the amount of sleep on average that they've got across the life span and at the end of the sort of life or in late life in the seventies and the eighties, we do a special type off pet scan to map the amount of amyloid in the brain. And then you just sort of look at those brain scans. Anyone on the street would not need any statistics. They would not need any training in brain science to see that one of the's maps is different to the other. It's like Sesame Street, and what is remarkable is people getting, you know, seven hours of sleep or less compared to seven hours of sleep or more. There's marked differences in the amount of amyloid that's built up. Now that's just associational evidence. But then, when you take it down to the level of animals, cities where they selectively deprive animals of either deep non rem sleep or they fragment their sleep,

you get an immediate amyloid buildup essentially within the brain, you start to have what looks like a sort of, you know, an amyloid sort of genic process that's happening. That's rats. So then we can all wave our hands if we want, because we would like to beat our chests and sort of, you know, say, I don't need my sleep and that's just rat stuff. Well, studies have now been done in humans where we will take a human being for one single night. We will take away the deep sleep, and the way that you do that is that you just play these auditory tones at night so they never wake up. So the total amount of sleep that they get is still eight hours. But I can just selectively exercise your deep sleep when that that sewage system should be kicking into gear.

Then the next day we do something that's really rather unpleasant. We do a spinal cord puncture, and we suck out some cerebrospinal fluid, and we can measure the amount off the two toxic proteins linked to Alzheimer's. One is called Peter Amyloid that we've discussed. The other is called tau protein, and we see the next day after one night of sleep disruption, a significant increase in circulating levels of amyloid and tau. For me, that was kind of like the turning point where I finally felt comfortable going on record and saying At this point, Folks, I really feel comfortable saying that your sleep is a critical component off your prevention of Alzheimer's disease. I really think the evidence is now, you know, in that direction and weigh in that direction is not just epidemiological. It's not just prospectively. Unger TUNEL studies which are better than cross sectional sort of epidemiological. It's not just causal in rats. It's experimentally causal in humans. After one night of sleep,

do you see variation there? Because one of the things that I find difficult with understanding all diseases and Alzheimer's would be sort of more so than even cardiovascular disease, because we still have so much less data is, there must clearly be enough variation between people that it's very easy at the head of a genius level to miss things that you would see in an otherwise homogeneous population. So, for example, when you look at the coinage of the term Alzheimer's disease, it's quite likely that that was coined based on a patient who probably had a P S and N one or two mutation such an early onset of the disease versus the disease we typically see. I mean, today those patients make up less than 1% and it's it's almost a different disease from the You know, these are people that are presenting in their fifties, and they're usually dead before their 60 whereas that 99% of the population are getting a sort of later on, said disease. And even, of course, then within that population, all of the variation with a po e Gina type.

It almost makes you want if there's different susceptibilities to this deprivation, because everybody and their brother can point to the exceptions to these rules, right? The person who did everything right slept like a baby every night and ends up down this one path. And then, of course, the person who does everything incorrect and seems to be completely fine, at least from the perspective of, you know, no obvious disease. So your analogy is really interesting because I don't really find myself hugely in the Emily Beta camp as the main causal driver. I think it's more of a result, but it's interesting what you pause. It is if it's more about the clearance of that than the generation of that, that would be a congrats view with this idea that, you know there could be other things on the back end that are driving this primarily. But of course, I think with Alzheimer's disease it strikes me as just so complicated because of the genetic predisposition, coupled with the multiple pathways that can seem to drive comparable insults to an otherwise incredibly sensitive organ.

I hugely cleave to the idea that probably what we call outside Miss right now is going to be sub typed at some point in the future.

That will imagine it's like cancer, right where in 30 years hopefully the rate of growth has slowed that it's not, you know, a pandemic. But yeah, you might have five subtypes or something for that.

That's right, you know, and I think we will see that, I think, and then we will start to patent match what features? I think the fact that sleep already, let's just call Alzheimer's disease, this strange Petra genius sort of mix right now that we feel uncomfortable about in terms of pinning one exact pathological ingredient as the causal trigger for that. In fact, I actually probably think Tao is if you

look at the date, I think the day are better off

without predicting cognitive decline at least than amyloid is. But the fact that you know, we've now found that insufficient sleep will also lead to tower aggregation, too. I think it is concerning him worrying. But let's accept that this Alzheimer's thing, this disease state is hatred, genius. The fact that sleep on we confined such a strong predictive sleep signal in terms of that risk, despite it, being such a diffuse gray matter ball itself of a disease must mean that the links between insufficient sleep and this hatred genius thing are, I think, probably quite strong. Otherwise, the dirtiness of the equation would be such that those associations would be far weaker rather than stronger. The fact that they're already present leads me to believe that when we do eventually subtype Alzheimer's disease, we will then find that there are subsets off sleep features that are deterministic off those subsets of Alzheimer's.

So, for example, deep sleep will be predictive of one form of Alzheimer's sleep fragmentation, which is more about sleep quality than it is about physiological quantity. You know, sleep fragmentation will be predictive off something else, another sort of subtype off Alzheimer's disease. Then I think, you know, basic

duration. Could matter.

I think they're probably have four pillars of sleep. There is probably regularity. How consistent is your sleep schedule from? Are you undergoing what we call social jetlag? Which is where you're bouncing around? You're going to sleep, you know, one AM than 10 p.m. And all over the map. So there's sort of regularity. There is tthe e continuity of your sleep. Is it fragmented air? You waking up many more times? Or is it just nice one long shot? That's a second feature. I think the third feature is quantity. How much sleep you getting? How much of the different stages of you are you getting?

And then independent of how regular your sleepers, how continuous your sleepers and the amount the quantity the final is quality and quality has come big in the last five years in the sleep field. In other words, what is the electrical signature of your sleep on dhe Just because you're getting eight hours of sleep doesn't mean that you're getting eight hours of good electrical quality deep sleep. And you know, I hope that we get the chance to speak about state of things like caffeine and alcohol, other substances of abuse that can make you feel like you're sleeping eight hours. But so quantity just fine. Quality poor. So to come back to your question, I love the way that you think about that problem, and I agree with it very much that Alzheimer's disease is probably going to be a hatred genius. I think the pathology already points to that. Its complexity, the way that sleep plugs into that hatred genius disorder that we call Alzheimer's is also going to be Hetrick genius in nature. Different sleep features will be predictive of different aspects of the amyloid pathology.

Cascade on were we just submitted a paper which I'm gonna blow now its surface of media sort of outlet, which hasn't been accepted yet. But we just tried to ask the question across someone's lifespan. If you book it them into 10 year decades and you ask what was the quantity and quality of their sleep from the thirties and forties, forties and fifties, fifties and sixties, so on and so forth. And then at the end of their life, you stick them in a brain scanner and you map how much amyloid is in the brain and how much towers in the brain, which is what we can do here at the sleep center. And then you essentially can. In a retrospective, Imanishi was sleep at certain times of life, more critical in predicting how much amyloid you will have late in life. So, in other words, are there certain decades during an adult's life span? Worst sleep is even more important for determining your How can you do that

retrospectively? So let's say you had this cohort of patients. Maybe at best you could, through questionnaires in for duration. But how would you be able to infer anything about depth or quality

so depth we can't do but quality? We can do so. We've got a set of standardized questioners that have bean essentially validated against gold standard what we call Polly sonography, which essentially is sleep laboratory grade recording with electrodes. And what we find is that those questioners have good predictive validity relative toe objective gold standard measures. So it's a hop, skip and a jump, but you can say, Look, the's subjective questioners seemed to go pretty well, hand in hand with sleep, quantity and quality. Let's take those questioners. And then let's ask off those patients what they were doing in terms of their sleep, quantity and quality in those different bucket decades of their life. And it has pool of the problems that you can imagine,

because this seems like a slightly better version of a food frequency question year, which your peers would be relying on to do the same question about nutrition. So

it's reliant on an individual. You know, it's got problems with history causing, you know, the further you go back, does that signal of accuracy degrade

how bigger the hazard ratios? Because I guess this is where one of those things where if sleep could account for 25% of this disease or if it if it increased the risk. But I say 25% would be a better way to say that it strikes me as unlikely that you could see that signal because that's not a big enough signal with all the noise you've just described. But if you were talking about a hazard ratio of six or seven or you know it's so funny today one of my kids asked me about smoking like, Why do people smoke? And this I couldn't resist going down the Bradford Hill pathway of. Unfortunately, he's 4.5, but he got a probably about a 12 minute lecture on epidemiology and the hazard ratio of small cell lung cancer and smoking. But the punch line in my story to him. Peter Attea, Ladies and gentlemen, Pita ta! I was trying to explain to him what it would mean to have a 14 ex increase in risk, which was basically what was observed in the first physician study of smoking. And you know, the point there is that it's such a massive signal that I mean a CZ.

You describe it. I love whenever you can get these things. It's statistics aren't necessary when you don't need the P value to figure it out. That's it. So does your intuition. And again, I don't want you to scoop what's already in this papers. If you can't speak about it, no problem. But Do you have a sense of that magnitude? And therefore, if even a crude backwards looking metric is directionally pointing you at something that you think, Wow, this isn't a subtle

change. Yeah, I mean, we're up in the region of, you know, from a 0.452 point six. So it's, you

know, it's in risk reduction for those doing it. Correct. OK,

yeah, So it's substantial. But what was interesting to me, which gave me more confidence, was that the windows of sleep sensitivity were, by the way, across the entire life span. Well, if you're getting less sleep at almost any point in the life span, the risk that you're going tohave higher amounts of thes Alzheimer's disease proteins in your brain is greater. That's what we find across the board. But what's interesting is that when it comes to those two different proteins out arm amyloid and tau, there are different decades that all predictive. So if it's just one global subjective bias in your questioner that you shouldn't see that result. So there is a sensitivity and specificity to these two different proteins that to me got me more excited that it transcended some of the limitations that are inherent in this approach, and also the fact that for amyloid you get a very strong predictive signal, you know,

thirties to forties and then again, sort of sixties to seventies. And for Tao, it's actually somewhere in sort of the starts in the fifties to sixties and then goes through until the eighties. So wanted a child years old, so we actually we didn't go back in terms of challenges because hard at that point, it's really difficult to feel confident about that data. You'd have to get parents who are not living at that stage. But to me, I think the fact that you got this strange

kind of and more heavily you've described by motile distribution for Emma

Lloyd Wright amyloid, which then lends me to believe that that result is difficult to explain by sort of just general memory biases, which would be kind of more of a Linnea approach. But I don't I mean, I think the point is that you know, with e evidence that continues to build in favor of this story, that insufficient sleep is a significant lifestyle factor in your deterministic ratio. Odds of developing Alzheimer's disease is ever stronger now on the fact that, unlike many of the other lifestyle factors, the mechanism underlying it has now being demonstrated causally, Inhumans and adults. And it's being done so acutely within a 24 hour period of time. That, to me just knocked me sideways and

the controls did not have. So if you controlled for everything except the perturbation, you didn't see the amyloid. Her tower rises are angels. Yeah, it's kind of interesting, too, because one of the reasons I've been a little less excited about amyloid there's two reasons. One is what can only be, I think describe is just the abject failure of the pharmacologic approach to Emma Lloyd. Reduction at our last counting. Oh, I don't want to be misquoted on this will include it in the show notes what the actual number is, but it's basically one Emma Lloyd antibody quasi success at Disease Stabilization to the tune of 2000 failures. That's one thing. The second is the autopsy studies of people who died without any clinical evidence of Alzheimer's disease who still have amyloid making me wonder if Emma Lloyd is necessary but not sufficient and therefore what if there's something else going on. And,

of course, the third thing I would now add, just based on thinking about it for two seconds. So this might not be well thought out is in the next couple of hours we're gonna talk about a whole bunch of other things that sleep does that are in and of themselves, completely devastating to your health. That also would feed into that, for example, the impact that negative sleep has on cardiovascular disease. And it's become quite clear that if you're doing bad things to your heart, you're doing bad things to your brain. And, of course, we're gonna talk about glucose disposal, hyper insulin enemy in all of those things, which also have a clear impact. So I think this would only strengthen the case that sleep deprivation is bad for you and bad for your brain. It to me makes it harder to tease out potentially the mechanistic links, although there's no reason, as you said, that it can't be multifaceted.

Yeah, I think there are certainly those conundrums where you see patients with non trivial amounts of amyloid in the brain, Let's say at postmortem, who are even only in the early stages of M. C. I of what we call mild cognitive impairment. They haven't transitioned

yet. I'm glad you remember to explain these things because I'm nodding away like I know

what. But that aside, I think three idea that it's it's necessary. Maybe not sufficient but necessary if you truly don't want necessary in your life. And if you're getting insufficient sleep, you're placing and necessary the where doesn't necessarily have to be.

You know, the analogy could be with lipoproteins. You know, there's a lot of alien, right? I mean, lipoproteins are absolutely necessary, but not sufficient for a thorough sclerosis. And so some people say, Well, there's no efficacy and reducing lipoproteins And I think part of it is it's defuse, right. You're only a tackling one of the four Constitutive elements for things have to happen for you to get after sclerosis lipoproteins being one. So that's actually an interesting idea, and it's a great argument for why would you want something that's necessary but not sufficient there? Why would you decrease your

odds? Yeah, I mean, you know, think about it like this. If you'll go. The two most feared diseases in developed nations. Right now, I believe a cancer and Alzheimer's

disease, and I would say it's in the other order.

Andi, Yeah, I think Alzheimer's is is, you know, top of the list that Do you want to de risk the probability of Alzheimer's disease in your life if you truly don't want to invite right to you know, this thing called Alzheimer's disease and invited in in the mail coming at you. But you're getting, you know, less than seven hours of sleep a night. You're not working in the direction that you wish. You're going against Alzheimer's disease prevention, and you're working well towards Alzheimer's invitation. People will often say, You know, how much sleep do you get and say, Look, I give myself a non negotiable eight hours sleep opportunity,

and that's not because I'm trying to practice what I preach. I don't want to be some poster child for sleep. If you understood what I knew about sleep on DDE, all cause mortality as well as most disease processes. You would realize that I am being nothing short of utterly selfish in my preservation of an eight hour sleep opportunity. I don't want to die young and I don't want sickness and disease in my life. My family, for example, has got a very strong history of cardiovascular disease, and we know that deep sleep is probably the best form of blood pressure medication that you could ever wish for.

That would be an easier one to study. I'm guessing we'll come to that later. Theobald sitio Iturbe deep sleep and then see the change in the conference.

Yeah, I think the point is, I think bash people over the head with this sufficiently. But the link between a lack of sleep and Alzheimer's now I think, is very strong. And what I find the positive about that is without times disease, just as you mentioned when it comes to pharmacological approach is we just don't have anything that looks robust right now. So medicine in many ways and especially for Alzheimer's disease, has started to shift from a model of late stage treatment toe early stage prevention. And I think I feel comfortable very comfortable, saying that one of the best preventative actions that you can take on the basis of the science right now is start to capitalize

on your sleep at night. So let's shift gears just a little bit and go back to the poly. Some let's explain to people, because we're gonna eventually have to talk about tracking these things. And I wantto bring up some of the sort of commercially available ways that people do that which I think, by definition, are still not accurate enough for people to, you know, compare them to their Polly Some. But if I came into your lab tonight and I was willing to go to sleep there and you would hook me up to N. E E G. What are the different patterns of brain waves, and how would you morphological e describe them and then bucket them by these stages? You've already sort of touched on a little bit. Is Deep Ram deep Prem Deep Non Ram, etcetera?

Yes. So upon falling asleep, human beings on DDE, In fact, all mammals will experience to different stages of sleep. One of them is called non rapid eye movement sleep. The other is rapid eye movement. Sleep. Non REM sleep has been further subdivided into four separate stages, which are unimaginatively called stages one through four. I think that's all that the sleep deprived people who are, you know, experimenting could come up at that time, so increasing in the depth of steep sleep. So stages three and four of non REM sleep. Other ready, deep,

restorative stages of sleep stages one and two of the light of stages of sleep. And then, on the other hand, we have rapid eye movement sleep, R E M sleep, which is named not after the popular Michael Stipe pop band, but because of these bizarre horizontal shuttling eye movements that occurred during the stage of sleep, these rapid eye movements. So you have these two different types of sleep, and they will essentially as you fall asleep here in at the Sleep Center of Berkeley, they will go into essentially a battle for brain domination throughout the night on that cerebral war between non Rem and Ram is going to be won and lost every 90 minutes and then replayed every 90 minutes to create what we call a standard cycling architecture of sleep. What we call a hypno gram of sleep. And so what you will see is that upon falling asleep, you'll go into the light stages of non

REM stages before we do that, Let's say before I fall asleep when I'm just laying in the bed, How would you describe my brain waves under the wakeful condition?

So at that point, what we typically see is that when you close your eyes, the back of the brain goes into what's called an alfa rhythm. So when you're awake, your brain shows this remarkably frenetic, high frequency electrical activity. In other words, your brain is going in terms of its brain waves. It's going up and down many, many times a second, and

he wasn't in the amplitude. And

the amplitude is very small. Which kind of his, paradoxically, you think if I'm awake than my brain is active. And so the size of those brain waves should be big. It's not. It's actually very small in his. The reason. Different parts of your brain a doing different things at different times. So those brain waves sort of are all canceling each other out. So the analogy would be if I were to dangle a microphone above a sports stadium. What I'm picking up is the signal from the crowd of 100,000 individual neurons that sit underneath it. That's how an E E G electrode is now before the game starts. That's wakefulness. And at that point, the 100,000 people in the Stadium 1000 brain cells. They're all speaking to each other at different moments in time.

So there's a lot of canceling,

so there's a lot of cancellation that not all coordinated, but it's very fast and frenetic, so I just get this signal that is very D synchronized. And it's not synchronous, so they're not summing their power together. So the size of that brain wave is not very big, but

but that's where the frequency

so high the frequency is high, meaning that yoke sort of going up and down maybe 50 60 times per second. Now, as you start to fall asleep, or actually even before you start to falsely as you're lying in bed awake, the back of the brain is the first part of the brain that really starts settle down. It goes into what we call Alfa rhythm when you close your eyes,

and I assume that's just because the occipital cortex is in the back and you've closed your eyes.

Brilliant. So the back of the brain visual brain, if you close your eyes. That part of the brain essentially stops processing the outside world, and it goes into its sort of default state. When it's awake, off slowed frequency, it drops down from maybe 50 times per second, down to about, let's say, 10 cycles

per second, but still relatively low

amplitude. What's still relatively low amplitude? Then, once you start to actually transition, when you make that bridge from the world of wakefulness to sleep, as you sort of cross through that window from one of those worlds to the next, something bizarre happens. And if anyone out there is looking to be listening to this and they have a bed partner, you can actually see this. Just look at that eye lids as they're falling asleep, and what you'll see is that their eyeballs start to roll in their sockets, and they're called slow rolling eye movements. Now we don't know why the eyes roll in the sockets like that, but it's the first sign that you're making the transition from the world of wakeful. Listen to sleep. We use it as almost an indicator of the transition into sleep. Now,

by the way, if your partner wakes up Sometimes full weight will wake up from that state, and they see you just looking over them in bed, staring at their eyelids. If you're in early in a relationship, it's usually the end of the relationship. It's just a point of note. Please don't blame me. Usually wait till you're married and then started. The divorce usually is harder to come by, so then you start to go down into the light stages of non REM sleep stages one and two. Then, after about 20 or so minutes, you'll go down deep into stages three and four

and owner and in one and two. Have we transitioned out of that Alfa Wave? I mean, where do we start to see the already failures and

fatal already happening in stage one In stage two, you actually go into feature activity, which is now down from 50 cycles per 2nd may be down to just sort of six or seven cycles per second,

and the amplitude is getting

a bit bigger. Is is getting a bit bigger Yem And then every now and again during stage to the way that I know that you're in this light a stage of non REM sleep. Stage two is that you'll get thes synchronous bursts of electrical activity that we call sleep spindles. That's the case, Wendell, on that sort of year where you get this, actually you get a nice, big, slow wave, like, almost like a single slow wave, and then you get this burst off asleep spindle. And we actually did this great project here at the sleep center where we did the sun ification of sleep and we we extracted brainwaves from human beings. And then we sort of, you know, smooth them a little bit with some sort of audio software, and then you can play them back.

And it's beautiful, because when you hear these sleep spindles, they are these short, synchronous bursts of electrical activity that last for about a second and 1/2 and they go up to about 10 or 15 cycles per second. So it's almost like that beautiful rolling our instead of in the Hindi language order. Oh, sort of like a cat pairing. So So you get these big, slow waves and then you get this ripple of a spindle on when you hear it on the speakers, it's just sensational. You get this. You know it every time I hear it. I mean, this is spine tingling stuff when you realize this is going on right now physiologically in someone's brain. And then from there you start to go down to the really deep stages of non REM sleep stages three and four. And at that point the brain goes into this incredible synchronous mantra chant of thes slow waves.

So the brainwaves slow down. You go down to maybe just one or two cycles per second. Very, very slow brain wave activity. But the size of those waves crashing on the beach of the court accepts it were they are huge. And the reason is this. Go back to the sports stadium analogy. Let's say that we're here at Berkeley and we're playing Stanford archrivals,

which hopefully you're gonna kick their butt fingers cross. Just make sure there's no band anywhere to be found.

It always does is a terrible decision, but at

that point they're chanting in unison, Will chanting in you so it's louder. But they're now making the same sound together, and you can actually hear

what's being said exactly. So now in that single microphone, you can hear. Stanford sucks whose Stanford sucks. So all of a sudden, all of for reasons that we are only now starting to understand the brain coordinates hundreds of thousands of neurons, unlike it does it any moment elsewhere. In the 24 hour period, hundreds of thousands of brain cells all decide to join hands, as it were physiologically metaphorically on. They all fire together, and then they all go silent. They all fire together, and then the old give science.

And what I find amazing about that, by the way, is how slow that frequency is. You're basically you could be. This could be it only happening once a second, right.

That's right. And that's why it got a terrible rap for 20 or 30 years because it actually looked not dissimilar to some aspects of coma. That's how slow those brain waves were. So sleep scientists were, you know, understandably fooled into thinking that deep sleep was a time when the brain essentially was just doing nothing. Now we realize the exact opposite is true, because it's during that deep sleep that you get essentially information transfer within the brain. It's a file transfer mechanism on the way to think about this is, let's say it's like long wave radio. If you're in the city, you tune into FM, which is short wave radio. You can pick up a bunch of signals than the further you drive out into the desert. Let's say here in California, you just lose those channels because the range from the tower is so sure that you just lose that range. But if you go on to sort of,

you know, the long wave radio stations, you can still pick up stations for hundreds of miles. Why? Because the carrier frequency off those radio waves is much slower, and so the distance over which you can transfer information is much further. Deep sleep is a brain state of long distance information transfer.

Is there morphological e a difference that you can see between stages three and four, which are obviously both Delta waves. But how do you distinguish those? Two?

Technically, no, the way it's defined is that what proportion off a 32nd period of time. And that's the way that we score sleep. I'll have you sleep for eight hours, but I'll chop up that eight hours into 32nd bits of information. On each 30 seconds, you'll get a sleep score, and then we add them all up. And what differentiates Stage three of deep non Rem sleep from the very deepest stage, which is Stage four non REM sleep is simply what proportion off that 30 seconds is consumed by that deep, slow brain wave activity. If it's sort of less than 50% than it's stage three, it's more than 50% Stage four. So morphological E no, although if you really look at it, morphological E on average. Yes, the waves are typically larger in amplitude and slower in frequency in

stage full than they are in Stage three. And do people always progress? Mon Atomic Lee through these or do sometimes people go 1243 ram, for example. No, you will have to go through three to get

before you have to go to three. To get to four, you have to go from two to get to three to get to four, with the exception off. Probably. Let's see two examples. One is pathological. If you suffer from narcolepsy, one of the things that typically happens is that you go from being awake straight into REM sleep, so doesn't finish the 90 minute cycles on. This will make sense. You go sort of state wants stage to stage 2334 Then, after about 70 minutes, you'll rise back up into Stage two. And then finally, you'll pop up into REM sleep, and then you'll have a short REM sleep period,

and then you'll go back down again, down into non REM. Sleep up, interim down into non REM. Sleep up interim, and you do that. I just said every 90 minutes. However, what changes is the ratio of non realm to realm within the 90 minute period as you move across the night, such that in the first half of the night, the majority of your 90 minutes sleep cycles are comprised of lots of deep, non rem sleep and very little REM sleep. But as you push through to the second half of the night now, the seesaw balance changes on the majority of those sleep cycles comprise much more of rapid eye movement. Sleep on almost no deep sleep, and that's why it's always dangerous when people say,

you know, I'm one of those who survives on you know 6 6.5 hours of sleep a night. I wake up, you know, 55 30 to get a jump start on the day and you can ask Well, let's say you're getting six hours of sleep. How much sleep you losing on? They will say, Well, according to your definition of eight hours of sleep, while I'm 25% off because I'm getting I lose two hours at the end of an eight hour night of sleep. So I'm sleeping 75. I'm losing 25%. Yes, and no. Because,

yes, it is proportionate. Exactly. So, yes, you're losing 25% of total sleep, but you could be losing up to 70% of all of your M sleep because it's the realms, the rich phase that you are short changing to get a jump start on the day. So you've got to be very careful when you try to think of your sleep dynamics. But to come back to your point, Terry. Yes, you always have to go through that linear progression. Narcolepsy is a standout case there. You'll usually go from wakefulness, sometimes immediately into rem sleep.

Very frightening. People don't experience, you know, logical, rational waking consciousness and then go immediately into irrational, hallucinogenic consciousness, which is what REM sleep is very disturbing when you speak to these patients, the other is, if you are horrific, Lee rem, sleep deprived or chronically sleep deprived. Occasionally you can make the transition straight into REM sleep. We see this in people who are abusing alcohol heavily, who are alcoholics. Alcohol will come onto this block your REM sleep. You can build up such a hunger for REM sleep that the brain says,

Well, tonight I'm gonna forego the non rem sleep. I'm just gonna go and feast on REM sleep straight away, this history says in the system maladaptive Lee. So that's a bad sign when you get history says like

that, that type of pressure does this explain? And maybe this is not even really correct. But you could see that someone who's constituent Lee sleeping six hours a night would suffer perhaps fewer of the memory consolidation issues because they're still getting much of their deeper sleep earlier in the evening, presumably where that hippocampal consolidation takes place and the lack of rims manifestations air just harder to see, like is that partially explain any of that, or is that is that even accurate?

It turns out that different types of memory rely on different stages of sleep at different times of night. So what we found is that you need sleep after learning to essentially hit the save button on your memories so that you don't forget. And for that it's all about deep non rem sleep. So as long as you were getting let's see the first you know, half of the night the 1st 5 hours, then it's likely that you may have been able to protect those memories. But here's the other problem that stage two non REM sleep, which actually happens most in the second half of the night. In the second half the night you're having either REM sleep or stage two. And in fact, if you look at those sleep spindles, they exponentially increased towards the end of the night. So you get most of your sleep spindle rich sleep in the last two hours of the night. The reason that's important is because you not only need sleep after learning to consolidate. To save those memories, you also need sleep before learning to get your brain ready in preparation, toe actually lay down new memories on there. It's staged to non REM sleep on these spindles. So what we've discovered is that the more of those sleep spindles that you have the greater of fresh mint off your memory encoding ability to so think about

it like that. And then this is a very beautiful experimental demonstration because you can surgically deprive people of each of those. And I've seen other talks you've given, of course, and in your book you touch on this where you could preferentially from an experimental standpoint, prevent somebody from consolidating memory, and you could similarly prevent them from forming new memory,

even though we can keep the total amount of sleep. Your assistant. So it's not a stressor. It's not that wakefulness. It's you can selectively excise, just like you said, individual stages of sleep.

What's the biggest detriment? That person's face clinically, with the reduction of rim?

I think right now, based on the weight of the evidence, it probably starts with mental

health, anything from depression, anxiety through disease,

anxiety, depression and then suicide ality. I think one of the most striking things that we've been seeing in our hands and other people have demonstrated to. This is a probably the second of the big area of work that we do here. Sleep centers, sleeping, mental health. You know, sleep is emotional. 1st 8 bottom line, period. And what you find is that in young teenagers, one of the strongest predictors off, firstly, suicidal ideation. In other words, thoughts of taking their own life,

strongest predictors of suicide attempts and, tragically, a very strong predictor of suicide. Completion is insufficient. Sleep on sleep fragmentation. Andi What we've been finding is that it's Ram's sleep that seems to provide essentially a form of overnight therapy, and it's Ramsey that resets or re calibrates the emotional networks in the brain. And there's a Siri's. There's a network off them that involves an area called the prefrontal cortex and particularly the middle part of the prefrontal cortex, which acts like a top down regulator of your emotions. So this deep emotional brain centers centers like the Image Villa, which is a centerpiece region for the generation of strong, impulsive, aversive negative reactions.

Anyone with a young boy knows with your

Magdala doesn't exactly if they have 1/10 temper tantrum in the middle of you know, the supermarket. It's because first, either prefrontal cortex, you know, has just not yet on what little of it that there is if they haven't slept well, is obliterated.

That's actually a really great example of one of the most obvious observations. Like we we talked, You know, I mean, any, any parent listening to this knows how emphatically you protect the nap. Correct, you know,

and it's for mental or emotional

for formal, just for behavioral health of the child, right? And it's sort of like your day revolves around the nap like, Can you go to Disneyland today? I don't know depends if we get the nap schedule and you know yes or no. And what you're basically providing is a technical explanation for something that is so empirically obvious. It's undeniable, and it's not the opposite right, So bear with me for a moment when it comes to the broader mental health stuff. You could easily construct an argument that says the era of causalities the other way, the person who is anxious, it's the anxiety that's keeping them awake. Now, my guess is, in reality, these two feet off each other constantly. So Europe's the right. You might be predisposed to anxiety that fosters lack of sleep. The lack of sleep amplifies and

boo boo boo. It's a two way street, but is the traffic flowing more dominant in one direction and the other? And I think this is what you're point you're gonna make.

But within the behavior of a four year old is a perfect example of you only need to screw that up one night. You give a four year old one bad night or miss one nap. I mean, it's very obvious how that translates into the behavior, so that would point in the direction of this. Sleep can really be the driver of the pathology if you want to use pathology to describe that, which, of course, is a strong term to describe, you know, outburst of four year olds. But but just to make the point right, that's that. That, to me, is one of the most interesting, albeit somewhat glib examples.

But I think it's so consistent. You know, I use that frequently where you often see a parent with a child and the child is crying and they look at you and they say, Well, they just didn't sleep well asleep As if there's this universal parental knowledge that bad sleep the night before equals bad mood and emotional reactivity the next day. And what's striking is that if you look at the data somewhere between infancy and even now childhood, not only do we abandon the notion that sleep is absolutely essential and non negotiable, but we start to stigmatize it with this label of laziness that your slothful or that your child is slothful, forgetting sufficient sleep and the reason that upsets me. And I am getting alone getting You'll love it animated, which is up for a British man. But the, you know, the the reason I do is because, firstly, you know, it took Mother Nature 3.6 million years to put this eight hour thing called a night of sleep in place.

And within the space of 70 years, if you look at the data, we've locked off almost 20 to 25% of that. You know, imagine coming along and saying, you know, in the next 100 years, I think what I'm going to do is for the entirety of human society. I'm going to reduce the oxygen saturation by about 20 to 25%. Do you think that's a good idea? And the answer is

no, no, it's such a great example. I'll pause for a moment just to tell a funny story that you and I have talked about off Mike, which is up until about 2012. I was in the I'll sleep when I'm dead camp and I know what led to that. It wasn't that there was a very deliberate decision at the end of medical school when a good friend of mine with all the best intentions, who was a year ahead of me. So he was now in that the end of his internship as I was about to begin mine, he said. And this is in the days when we didn't have the 80 hour work week requirement in residency. So we averaged, I think, about 100 and 14 hours a week in the hospital. So he said to me, Look, Peter,

you're you're signing up for, you know, whatever. 57 years of this thing, if you spend every moment outside of the hospital sleeping, you would still be tired The only difference is you wouldn't have any fun. So make sure you live every moment that you're not in the hospital to the fullest. And so for me, that basically meant if I was in the hospital, I was swimming. I was going out with my friends. I was trying to meet girls, like doing anything, everything such that during that period of my life. I just know because I was pretty adamant about recording how much time, like I was very wed to this idea that 168 hours in a week,

if I'm spending, you know, 114 of them here, and I spend this money driving and I spend this money getting groceries and I spend this money swimming and bubble bubble block, I I think I was about 28 hours a week of sleep, so it wasn't four every night because you have none, and then six and then three and then ate like you. You could binge sleep from time to time, but it was pretty much 28 a week. I'll come back to some of the implications of that, but fast forward a few years I'm talking to a good friend of mine, Kirk Parsley, who's a physician who, like you, is adamant about you know, the importance of sleep.

And we're having dinner one night and he says he's challenging me on this and he says, So let me get this straight. You just decided that you're gonna sleep half of what is evolutionarily program. And I said, Yeah, because does it strike you as odd that evolution would have designed us to spend 1/3 of our life, not mating, not watching out for predators not hunting for food but doing this thing for some other purpose. Do you think that thing must have been important? And it was such an obvious argument, But it really overnight changed the way I thought about this, which was evolution went to great lengths to do this and superficially at great cost to us, right? I mean, you could argue. Well,

imagine you didn't need to sleep, and you could spend 24 hours a day foraging for food or a mate or some other thing, but it didn't. So it's sort of it's sort of like there's probably a reason we're not an aerobic to your point. About reducing oxygen saturation by 25%.

You know, if you were to think about that, you know, during sleep, Justus, you said you're not eating. You're not finding food. You know, finding a mate, you're not reproducing, you know, caring for your young, you're vulnerable to predation on any one of those grounds, but especially all of them put together as a collective, completely anti evolutionary. It sounds like the dumbest thing and, you know,

often said, and it has been said before, if sleep doesn't serve an absolutely vital set of functions, it's the biggest mistake that the evolutionary process has ever made. And we now realise, from this constellation of evidence that Mother Nature did not make a spectacular blunder in putting this thing coordinate our sort of need of sleep in place. It is the greatest life support system that you could ever wish for. It is a remarkable health insurance policy, and what's great is that it's largely democratic. It's mostly free. And in terms of a prescription from a doctor, it's largely painless. So I almost wanted to title the book. Consciousness is overrated, or just sometimes dot, dot,

dot consciousness is overrated. But when you really look at the evidence in terms off risk de risking just about every disease that is killing us in the developed world, it's very hard to look no further than sleep. And that's why I don't want to trivialize diet and I don't want to trivialize movement and activity. But what I would say is that if you want to put sleep up against either one of those two and kind of play the whole head to head game, which I don't think we need to do here, I would simply say that sleep is the foundation on which those two other things sit. It's not the third pillar of good health. I think it is the founding.

That's a really interesting way to think about it, because I typically describe four pillars or five. If you include all of the exogenous molecules that you could lump together but another way to think about it, which again, I don't think it's necessary that right way to think about it. But sometimes it makes the point. If you deprive yourself of food, how long can you survive? Well, we have one person up to 382 days, even someone who's as Lena's. You could survive 30 days with no food. How long could you survive without water? Depends greatly on the temperature, etcetera. But you could make the case that deprivation of sleep would result in the quickest reduction of health. Certainly more than not eating or not exercising for a period

of time on their studies have been done in

rats. And actually, we know some of this from humans who have been tryingto, in fact, didn't the Guinness Book of World Records. I came here. If I read this in your work, they've actually banned attempts at longest period of sleep deprivation. So I mentioned your

time when you could still try and beat the world record of sleep deprivation and got up to about sort of. I think the last true effort was about 24 days, but I think it was debatable that one. But based on the weight of the scientific data, the relationship with between sleep loss and mental health, sleep loss and cancer, sleep loss, cardiovascular disease, sleep loss, a metabolic syndrome, Guinness started to feel very, very uncomfortable. And then when suicide came on the table, it pulled it. So in other words, think about this. You know, there was a gentleman. Felix Baumgartner. I think his name was who sponsored by Red Bull. Went up in a capsule in a water balloon to the outer surface off our planet.

This was about four years old years. It's

remarkable. He opened the door and then he jumped out and he fell back down to Earth at over 1000 kilometers an hour. Using his body alone, he broke the sound barrier and he successfully came back. And now Guinness says for that just fine. However, to sleep deprived yourself no much more unsafe. We're not going to

let it happen. You are allowed just to put it in context. There a lot up to 12 jumps off Niagara Falls, basically. But that's OK, but no, no, you're not gonna That's such a great point. I want to go back to one other thing to close the loop on this and again. I the listener, may say, Boy, this is where there's a lot of stuff going on here, But but there really is like, this is I think you have to have a lot and I'm trying to think about all the questions I can ask that others would have if you took two individuals who were sleeping six hours a night. If you have one person who, just for the argument's sake,

is doing it from 9 p.m. To 3 a.m. and another person's doing it from midnight to 6 a.m. would you expect, Or even if it was, let's make it even more clear. It's the same individual, but you do it over a period of weeks. You transition them from 9 to 3 versus midnight to six. Would their sleep wave cycles look the same? Would they still be truncating the same amount of rim at the tail end of that? Or would they start to do some forward truncation

forward truncation. So essentially, what happens is that your brain has a different hunger or different appetite for different types of sleep. So think of those different stages of sleep like a finger buffet and at different times of the night, that buffet is going to be sort of, you know, consumed more heavily in terms off. You know, the deep, non REM sleep phase, which would probably be the hours from 9 p.m. Through until about sort of 3 a.m. That's really the the window of preferential appetite for your brain when it comes to deep, non rem sleep. That's when it will preferentially eat at that type of sleep. But then, from about 3 a.m. Through until about midday, then the brain shifts in terms of its pattern. If you let people just sleep it out.

You know if if you look a TTE extreme owls who we should speak about current types at some point. But people who you know like to go to bed very late and wake up very late, essentially the then the buffet is gonna get hit hard in terms of REM sleep devouring. So I make that point that your brain has different taste sensitivities to non REM and ram across the 24 hour clock face because it means that if you're short changing your sleep by two hours, but you're doing it by going to bed very early and waking up very early, then what's going to happen is that you're probably going to be losing most of your RAM sleep because most of your RAM sleep happens in the late morning hours, and you're already awake by three or 4 a.m. in the morning. And so you're not getting the chance to get into those realms. Sleep rich phases

and which of those patients would develop Maur appetite for sleep the subsequent evening. The person who was deprived and you know why I'm asking, by the way, it's exactly what we were talking about earlier. It's this jet lag question, right? If you know you've got that flight and you need to force yourself to sleep at a time zone, that's not right. I'm just now thinking about Well, I always do the 9 to 3, right? Would I be better off doing that? In other words, I'm depriving myself of Ram would be better off just describing Just

risk, depriving yourself of RAM. But you're also still depriving yourself of total sleep as well. You know when it gets the like modeling and you know, there there's some anything that that's an interesting model, and I think it does work that you can try to in the week before you start to fly. Let's say you're going. I'm going home to London, which essentially is eight hours ahead. So I need to now essentially start to sort of. By the time I'm waking up, people in London have already been awake for essentially eight hours, so I need to start to get myself on the schedule. So I start to wake up, you know, 10 minutes earlier, for about five days before Andi,

you know. So I'm only about an hour shifted, but it helps. And then the morning off the flight, I'll wake up, really? Especially early on. Then I won't that make the mistake that everyone makes on those transatlantic flights, which is they sleep in the second half of the flight. You shouldn't do that. You should sleep in the first half of the flight, which is when most people in the UK are asleep. And by the middle of that flight, most people in the UK that's their timeto wake up. And so you should be waking up that time so that you build up enough of this sleepiness pressure by the time that you want to get to bed, once you've landed that evening in London and this won't make too much sense right now and I think we'll we'll speak probably a lot more about this when we speak about caffeine and Tennessee's pressure,

but that but to come to your point, you're building up what's called sleep pressure. The longer that you're awake, the Morris that's healthy sleepiness that builds up. But to come back to the real question. And yes, just because you sleep, you know, five hours from one point in the clock face maybe earlier in the night to sort of early in the morning, versus five hours late in the morning until later in the that day, the type of sleep that you get will not be the same. You will be selectively shortchanging yourself off sleep either of deep sleep or of REM sleep on either side of that

equation. This points out another interesting observation, which I do want to spend some time talking about wearables because, of course, you know, we're both wearing our wearables at the moment, and I think we both acknowledged that Look, I mean these things, they're still not quite at the level of the poly some and maybe they never will be. I mean, that's a very difficult thing to replicate from, You know, something on your wrist or your finger. But it's so funny. This might explain an observation I always experience when I come from New York back to California, which is I generally try to stay on California time even when I'm in New York going to bed later, waking up later and in California.

I'm a very early sleeper in an early riser. So even if I'm trying to keep it at eight hours and eight hours, and I can do that very well in California not as well in New York my first night back, even my 1st 2 nights back in California, I have much higher, deep sleep, and that would explain it. It's this phase shift that I'm capturing This I mean, last night was because I came back from New York last night, you know, went to bed it. I don't know 8:30 p.m. And got up at five or 4 30 or five in the morning.

So you have had you deep sleep exactly. So you've dragged your eight hour window if you think about the sort of eight hour window and you slide it back on the clock face from midnight to 11 p.m. to 10 p.m. In fact, 9 p.m. You're dragging that eight hour sleep phase back closer into the deeper sleep rich phase that the deep, non rem sleep that you want. So what your sort of ordering will be telling you is you got more deep sleep on. Perhaps you may actually see a little bit of a reduction in and ram sleep As you go to New York. You may see the opposite as you sleep later in the morning, you'll get

really do matter, which is I get it. You know, it pisses me off, too. I'm like I didn't get much deep sleep and I got more REM sleep and not that room is bad, but I'm generally more upset by the dearth of deep. You know, it is interesting. It's now, really, I really I really need to think about that. Because, of course, on some level, our body is responding to cues in the environment. It's not just responding to the intellectual knowledge that hey,

in California, it's this time it's time to go to bed. It's I mean, light is playing a role. Meal timing is playing a role, which means I want when I want it. Definitely talk with you about this because this is to me to such an important topic. And then, of course, the accumulation of a dentist scene and of course, the military. So

by the way, I would just say that, you know, I think realms sleep. Some people I have this kind of by motile distribution of questions. Some people will say, How do I maximize my REM sleep? And I say, Why do you want to maximize your REM sleep? Well, that's dream sleep. And that's the good stuff, right? As if you know, it's like saying, you know, how do I maximize the amount of yolk in my egg?

You know, do I get a lengthy or can I go the Austria jag, Whatever it is, I don't know what the analogy is. And the question is, Mother Nature's found this equilibrium don't mess with it is the Da Vinci Code of sleep and stick to it. You good to go. But also then other people will say, you know, how do I get Maur Deep Sleep Board? You know, I you know who'd get upset by that lack of deep sleep to come back onto REM sleep and how important it is the studies have been done were, firstly, they deprived. And by the way, the studies have never bean done again since the 19 eighties.

And they probably never will be because of the ethics regarding them, because they are just so devastating that we probably won't be allowed. Rightly So, I think, to do these two, these two animals ever again. But they essentially deprived animals of sleep until they died. And what they found was that rats will firstly die as quickly, if not quicker, almost by about 20% from total sleep deprivation, as they will from total food deprivation. So if you want to put

sleeping, that's interesting. That they're gap is much narrower because for humans, the gap is is very. You'll die way earlier from sleep deprivation than food deprivation. Unless you're, you know, the leanest person

on the planet. And there is a tragic disorder that describe a little bit in the book. It's a very rare, genetically inherited disorder called fatal familial insomnia, and it's really the only evidence short off the disgusting travesty that is total sleep deprivation used in certain countries for interrogation tactics that we know of that has led to death. But withstanding that this disorder fatal for millions insomnia says it in the name that essentially human

beings were how how older people typically survive.

It usually takes about 18 to 24 months before they die. But the problem is, this is not. They wake up one day and they are no longer Stephen a gradual thing. So it's kind of like it. Masqueraders. Just typical insomnia. First restless nights for the 1st 2 or three months. Then it gets worse than you're only sleeping four hours than you know by month 12. You already sleeping two hours.

How much of this is genetic versus environmental versus we don't know.

It's strongly heritable that we know. So it's within the men. DeLeon sort of, you know, pool of genetic disorders, and it's testable. We know that Jean. Interestingly, it's what seems to only two single Yeah, and it's a prion protein gene abnormality, which is, if you don't know about prion proteins, you may have heard of mad cow disease, which was rife in the United Kingdom. That's another thing. That's another prion protein

disorder that's why you can't donate blood.

And it's also why, Yeah, I'll probably forget half of what I've been saying and start repeating myself because I've bean vegetarian for about 12 years. But before I went that route, I think I definitely was in the phase of eating beef when it was filled with thes frowns at me. United Kingdom. So my brain is probably Swiss cheese at this stage, but essentially this disorder fatal familial insomnia. It gives us some degree of disease proof that insufficient sleep is fatal for human beings. But we knew it in these rats cities because these rats would die as quickly from food deprivation as they did from sleep deprivation. But the most striking thing was there made it a second round of studies. They selectively deprived them of either just non rapid eye movement, sleep or rapid eye movement. Sleep on. What they found is that the rats were dead within about 9 to 10 days. With total sleep deprivation. They would dad within just about the same period of time from realms. Sleep deprivation

duration was kept constant or also reduced.

It was still reduced

somewhat, but you could probably look at a control that had the same duration without a selective.

Yeah, and there's a what's called a yoked paradigm. It's a very clever technique. Were you can mimic the total amount of sleep deprivation in one other animal, but the other animal is still getting the chance to get rammed sleep. So Ram sleep selectively removed. The rats died basically almost as quickly as they did from total sleep deprivation and then non REM sleep deprivation was deathly. Ultimately, it just took longer. Took about 20 days.

Total sleep deprivation Let's just say, for argument's sake, you die in nine days Sleep reduction, but selective realm deprivation. You die in the same period of time, basically, and sleep reduction. But deep deprivation. You live

maybe twice a long. Yeah, so everything definitely everything fatal. Just that one takes a little bit longer to kill you than the other. And what I find either strange or exciting about that is if you look from an evolutionary standpoint, those two types of sleep did not emerge. At the same time, we only have observed true rapid eye movement sleep in birds and mammals. We don't see true RePet eye movement, sleep in reptiles, amphibians, fish or insects. Now birds and mammals evolved separately along the evolutionary path from amphibians, fish and reptiles. So what this means is that when we went from the transition from being reptilian thio, either avian orm, um,

alien. That's when REM sleep emerged because we see non REM sleep in every species, even in insects, we can observe something of looks like non REM sleep in reptiles, fish, amphibians, birds and mammals. Every one of them has non rem sleep. Not every one of them has rams. The only birds and mammals have REM sleep. In other words, realm sleep is the new kid on the block in the time course of evolution realm. Sleep first emerged later in the course of evolution on Dhe. Secondly, what's kind of wonderful is it emerged twice independently wants in birds and once in mammals. So you could argue that well,

if deep non rem sleep, which is much more evolutionary from an evolutionary perspective, it's in much older form of sleep, wouldn't it be the much more necessary fundamental one? And therefore, wouldn't you die sooner?

Know it? Say it, Say it, Say it seems the opposite because you'd say well for the same reason that the cockroach can survive the nuclear disaster. The avian mammalian pathway is more evolved, narrow Nelly presumably, and therefore probably requires something essential in rhe m that when it deprives you, it takes away your superpower, which is a cortex,

and I think that's exactly what it is, which is when you look at anything that has essentially a complex nervous system. Maybe that's where the pressure for this thing called REM sleep emerged, even though we know that non REM sleep actually supports many essential central nervous system functions like synaptic pruning and some great sort of neural think you know, the lymphatic system clearing up.

It's sort of similar to your oxygen analogy, which is you when you go from being an Anna robe to a faculty van, a robe to an a robe, who's gonna be most sensitive to oxygen production?

Exactly. And so you know, it's always a dangerous scientific hypothesis where you can argue it both ways, but I always found that interesting and it's uncommitted. But I just wanted to note that for, you know, 20 minutes ago in kind of in Defense of REM sleep that you know, if we should, it will be worried about the amount of deep sleep that we're getting. Absolutely. But we also need to be worried about how much REM sleep that we're getting, because from a pure mortality risk standpoint, Rem sleep is arguably even more important than normal

and will come to this later. But my recollection of the literature is, and I think you even alluded to this earlier. Ethanol's biggest hit is gonna be on Ram,

isn't it? Hands down. This is where we come on to substances that ah misunderstood and misused when it comes to sleep.

Now, before we go there, Matt, look for me. I don't need any more of a case in the importance of sleep. And I think, honestly, the Alzheimer's thing alone should be sufficient for anyone to take this seriously. Because certainly my patients, that's the single most important thing to them now. There are some of them that are more high risk, you know, people that have, you know, a plea for Gina type that's in the, you know, the direction that would increase risk or family history.

But I don't think I've met a patient yet Who doesn't say on some level, Preserving cognition is their single highest priority in life. That said, Can you spend even just a minute? A couple of minutes? It's the drive. After all, we have all the time in the world making the case a similar case in the presence of cardiovascular disease and cancer.

Yeah, and I want to touch on that point before we go on about this Alzheimer's disease risk. You know, a lot of people out there maybe having this sort of like sleep machismo moment where they have this braggadocio attitude of getting insufficient sleep. And they say, Look, I'm in my fifties on, you know, I'm fit as a fiddle on My cognition is razor sharp and I sleep five or six hours a night. So we've got, you know, heads of state, for example, who are saying this. People who you know, have a huge impact on the public, and they're saying these things,

and it makes me sad because you can look at two other heads of state who were very vociferous about their proclamation off the uselessness of sleep. Margaret Thatcher and Ronald Reagan, both of them, were chest beaters when it came to insufficient sleep. They were very proud of saying that they only got four or five hours of sleep, that they were immune to the effects of insufficient sleep. That sleep was for the week and that you can sleep when you're dead. Which P S is mortally unwise advice based on the evidence, The shorter your sleep, the shorter your life. That's what all of the studies tellers. I don't think it's coincidental now, looking back that both of them went on to develop Alzheimer's disease. And it makes me so sad because I saw pictures of Margaret Thatcher in an enfeebled state of dementia. And I'm just thinking, you know,

if only when she was, you know, in her fifties, Aunt had that bravado about sleep. If she could see herself in that bed in that later state of life in such a crippled mental, cognitive functioning state, would you be so brave about it? And I would hope that she wouldn't that humility would come into place. So that's the first thing about I think, the insufficiency of argument and people rightly being frightened, having the daylights friend out of them about preserved cognition. You should have that regarding your sleep. The other one, though that frightens me, too, is the other way that a lack of sleep can get You is not chronically across the life span without Simon's disease,

but acutely with car crashes. And I know that will come into this at some point to. But the only thing I would say is that I get many emails from people who've read the book. Two months ago, I got an email from a gentleman. I won't name him on Dhe. He was in his late thirties, and he described how, three months before that he had lost his wife and his 18 month 18 month old child in a car crash on it later became apparent that the person who hit them had basically been surviving on about 5.5 hours of sleep for the two months prior that they had had what's called a micro sleep. They actually lost control of their car at 60 miles an hour at a moderate drift angle. You are essentially in the next lane within less than a second, and you're in the ditch after a second, and they went straight head on and now he was going to have to raise his four year old son by himself without the wife that he loved without the 18 month daughter that they'd invested in. Because someone perhaps had heard from someone vocally in the public that surviving on five hours of sleep was something that was okay, too. D'oh!

And to me, that just breaks my heart. I just don't feel comfortable, you know, having the responsibility like the head of a state of a country. And then speaking about this thing, this kind of magic attitude of insufficient sleep, because that's what it can lead to it can lead to the travesty of the explosion of a nuclear family.

And my guess is, even though it's gonna be very difficult to actually quantify this, I believe that the story you just shared is an especially tragic, poignant example of something that probably occurs much more than we're able to quantify. I sometimes say to patients, You know, the four Horsemen of Death would be these big chronic diseases that kill us. But but we could never forget accidental death. And then when you look at accidental death, how do you quantify it? Well, It turns out that three forms of accidental death form 80% of them, and the biggest among them is motor vehicle, right? And so the question is, what can you do to reduce that risk? So if you look at it some form of distraction and I've included sleep deprivation that but now I almost feel like they need to be separated out.

Distraction, meaning your putts and with your phone, your check in ways you're doing something you shouldn't be doing with your phone, sleep deprivation, ethanol, failure to wear the seat belt and reckless driving. I mean, that basically accounts for it. It wouldn't surprise me if that's that sleep deprivation bucket is bigger than we think.

I mean, we've got some decent data on this and firstly, what we know is in the hour that we've bean talking Already, numerous people have lost their life in a drowsy, driving related accident. Based on the statistics, we know that already on the way that we can tell that is both from speaking to the people who are involved in the accident. But you can also pick this apart from the dynamics of the accident as well, and Here's the problem when you are under slept that we're not talking about a night of total sleep deprivation. That's where you fall asleep at the wheel, and that's the obvious one, the much less obvious one. But the much more common one is what we call micro sleeps. So when you are trying to survive on seven hours of sleep, six hours of sleep and it really just takes that little of a dose, by the way, haven't forgotten our cardiovascular question.

I welcome back to it, but what you essentially have are these small lapses we call them micro sleeps, where the eyelid will partially close and you can pick this up on a camera on. They've done the studies systematically, where you dose people from getting nine hours of sleep to eight hours of sleep. 76543 for one week, two weeks, three weeks. The studies have bean essentially looked at sliced and diced Parametric Lee that probably the best that he's done within the field of sleep, and so we know them very well. What your lapse rate is, what your micro sleep break is, and what you find is that the island partially closes. On that point, you no longer react on. The reason I'm bringing this point up is that drowsy driving accounts for more accidents on our roads than either drugs or alcohol combined combined.

Now, I'm not condoning drink, driving or driving, and he created under any circumstance. What I am saying, however, is that first, the drowsy driving is a huge part of this problem on our roads, and the reason that it's not just problematic is because it's usually much more deathly. When you are drunk, you typically react, but you react too late, so you do something, but it's not enough, and you crash when you have a micro sleep, it's a project to do nothing.

That's why drowsy driving is more fatal than drunk. Driving typically is because there is no snow affliction of break. There is no application of break. There's no course correction of steering wheel angle. There is nothing. There is simply a car with no one in control, and it's a two ton missile on the freeway at 65 miles an hour, with no one in charge. This is why I feel really uncomfortable about the idea of public proclamations of insufficient sleep. And I get that. And you know, there are people, sports stars, p all sorts of people who I respect hugely on Dhe. And I haven't immense amount of sympathy for where they're coming from, because I think there's a lot of public pressure.

Thio be this out spoken. I'm gonna be crushing it on the sports field on. Then I'm going to be, you know, back in the gym the next morning and sleepers for you know, X Y and said, Who cares? But then you get someone in a car and you hear a story like that. I can't help but just

have my heart broken. But I think you know, Matt, your work has come along at a really interesting point. I mean, I have to be honest with you. I remember when your book came out and my initial thought, Waas does the world need another sleep book? Because there's 2000 of them out there, and I think there's two things that are different. The first is your book is exceptional. Actually, I'd say three things. Your book is exceptional. The third is your understanding of the topic, and your credibility is exceptional and those aren't necessarily synonymous. You can have really credible,

thoughtful people who write a book. But the book itself isn't exceptional or it doesn't hit the tone and some and conversely, you can have someone who puts together a good book, but they themselves don't have the credibility. I think so. You could take credit for the 1st 2 I think the third is is the little bit of luck, which is I think we're at a point in time where people are ready to hear this. In other words, if you the exact same professor wrote the exact same book 20 years ago, I'm not convinced it would have the same impact it is having today. Now, I don't know. You probably have a better sense than me. I don't know exactly what accounts for that difference today. Is it that today we are more interested in, You know,

the thin end of the wedge for this might have been our interest in performance. Maybe that is the thing that first got people to think about this which is Well, wait a minute. You know if I want to be better at X, Y and Z, whether it be my sport, My craft, My whatever is sleep a tool. I need to be optimizing the way people have for many years realized. Hey, what you eat and how you exercise absolutely impacts your performance. So I'm not sure what it is. But I I have a feeling and I can't have this discussion with my daughter a couple of weeks ago that we will look back at the way we think about nighttime electronics, sleep deprivation and things like that. We will look back at that in 20 years. Hopefully sooner the way you and I would look back at,

you know, a smoking mother being told by her doctor smoke this brand versus that brand like we can't even fathom that that was a discussion that took place as recently is about 1966 in the United States. And yet we're kind of in the our infancy in the dark, from a clinical perspective, from sort of a public health perspective, we and functioning on this.

So firstly I mean so much great stuff to impact the I think you're absolutely right. I think the success of the book is largely despite my my ability to write and convey ideas. I think what happened is that it was a perfect storm. Were

there is I gave you. I gave you 2/3 of the credit. Thank

you. Think I don't know if I can take them. I feel so ashamed. But I think the middle point is the erosion of sleep. Time has hit an all time high. We are now sleeping less than we have ever done in what seems to be the history of our species. Now we can't say that for sure. But what we certainly can say is that back in the earliest record that we have of a systematic questioner which was in 1942 by Gallup. What they found was that the average American adult was sleeping 7.9 hours a night. Now that number is down to six hours and 31 minutes. That's the average 6030 woman. That must

mean that. How linear has that declined? Ben? Matt has that non Selenia. Yeah, it's accelerating

isn't accelerating. Yeah, So I think you've had this ballistic erosion of sleep time, this decimation of sleep throughout industrialized nations. And it's not just America by the way Japan is even worse. It's down to 6021 minutes. You know, my home country, United Kingdom. Not much better. 6049 minutes. And these averages, you know, you've got to imagine that, you know, at least 1/3 of the people are probably trying to survive on five hours of sleep. Certainly during the week they are It's that plus this incredible explosion off sleep science over the past 30 years.

And this perfect storm has led to a collision where society is sleeping, less disease and sickness has bean escalating in a manner that you know we've almost never seen before and the knowledge of what sleep is doing. We know far more now. Sleep is not just curing sleepiness. Sleep is actually supporting. There is no physiological system in the body. And there is no operation of the brain that isn't wonderfully enhanced by sleep. When you get it or demonstrably impaired when you don't get enough, that knowledge and the causal knowledge of sleep in that it's not just associational, it is many off them are causal links with those disease states, I think, led to this ability to write this book at this time. That felt as though it was somewhat unequivocal that it was very difficult toe argue with you. You can pick apart once three from another. But when you build that blueprint manifesto when you build the scientific, cold,

hard, rational, emotion free case for sleep, it's very difficult to argue with. And it just happened that we were at that time in our human history with sleep, and we were at that time in our scientific journey regarding our understanding of sleep. I think that's why the book felt like it was. It needed to be

written and needed to be written. Now, for what it's worth, you had many moons on the front and back covers. So my little

Ed was delighted. You love? Yeah, he's probably read from literally from cover to back cover

everything. Nothing

in Victoria. Exactly. That's just fine. I asked people, They please, You don't have to read the book. You just have to buy it,

Okay, there's like literally 100 more things I want to ask you about. So can you make the case for why cardiovascular disease is worsened by or accelerated by sleep deprivation? And then same question. I'm gonna ask you in a moment for cancer, you can find all of this information and more. Peter Tia MD dot com forward slash podcast. There, you'll find the show notes, readings and links related to this episode. You can also find my blogged at peter tia MD dot com. Maybe the simplest thing to do is to sign up for my subjectively non lame once a week email where I'll update you on what I've been up to. Most interesting papers I've read and all things related to longevity. Science, performance, sleep, etcetera on social.

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